Gestion des hypoglycémies après le bypass gastrique [Management of hyperinsulinemic hypoglycemia post-gastric bypass surgery].

Gastric bypass surgery is an effective treatment for morbid obesity, allowing a substantial weight loss together with an improvement of the cardiovascular and metabolic comorbidities, particularly the glucose control. However, after gastric bypassing, an imbalance between sensitivity and insulin secretion may be observed. This disorder gives rise to hyperinsulinemic hypoglycemia (late dumping syndrome) and is characterized by a dizziness that can be disabling. This problem must be distinguished from conditions provoking similar symptoms, as for instance the early dumping syndrome and the food restriction-related hypoglycemia. Since all these conditions need a particular management, their distinction is essential.

Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.

BACKGROUND: After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. METHODS AND RESULTS: We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87,000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. CONCLUSIONS: We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.

Extent of hypoattenuation on CT angiography source images in basilar artery occlusion: prognostic value in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). METHODS: BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at ≥8 versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0-3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0-2). RESULTS: Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS≥8. Patients with a pc-ASPECTS≥8 more often had a favorable outcome than patients with a pc-ASPECTS<8 (crude RR, 1.7; 95% CI, 0.98-3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS≥8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8-2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5-0.98) and functional independence (RR, 2.0; 95% CI, 1.1-3.8). In post hoc analysis, pc-ASPECTS dichotomized at ≥6 versus <6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2-7.5). CONCLUSIONS: pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.

Decoupled post-glacial history in mutualistic plant-insect interactions: insights from the yellow loosestrife (Lysimachia vulgaris) and its associated oil-collecting bees (Macropis europaea and M-fulvipes)

AimWe take a comparative phylogeographical approach to assess whether three species involved in a specialized oil-rewarding pollination system (i.e. Lysimachia vulgaris and two oil-collecting bees within the genus Macropis) show congruent phylogeographical trajectories during post-glacial colonization processes. Our working hypothesis is that within specialized mutualistic interactions, where each species relies on the co-occurrence of the other for survival and/or reproduction, partners are expected to show congruent evolutionary trajectories, because they are likely to have followed parallel migration routes and to have shared glacial refugia. LocationWestern Palaearctic. MethodsOur analysis relies on the extensive sampling of 104 Western Palaearctic populations (totalling 434, 159 and 74 specimens of Lysimachiavulgaris, Macropiseuropaea and Macropisfulvipes, respectively), genotyped with amplified fragment length polymorphism. Based on this, we evaluated the regional genetic diversity (Shannon diversity and allele rarity index) and genetic structure (assessed using structure, population networks, isolation-by-distance and spatial autocorrelation metrics) of each species. Finally, we compared the general phylogeographical patterns obtained. ResultsContrary to our expectations, the analyses revealed phylogeographical signals suggesting that the investigated organisms demonstrate independent post-glacial trajectories as well as distinct contemporaneous demographic parameters, despite their mutualistic interaction. Main conclusionsThe mutualistic partners investigated here are likely to be experiencing distinct and independent evolutionary dynamics because of their contrasting life-history traits (e.g. dispersal abilities), as well as distinct hubs and migration routes. Such conditions would prevent and/or erase any signature of co-structuring of lineages in space and time. As a result, the lack of phylogeographical congruence driven by differences in life-history traits might have arisen irrespective of the three species having shared similar Pleistocene glacial refugia.

La diversité des motivations des employés publics : recherche exploratoire dans un contexte post-bureaucratique en Suisse

Durant les dernières décennies, la recherche portant sur la motivation des fonctionnaires a été dominée par deux courants théoriques : l'approche dite des choix rationnels, et celle portant sur la motivation au service public. Dans l'environnement post-bureaucratique actuel, cette vision simplifiée, qui reflète aussi dans une certaine mesure la dichotomie « public-privé », ne reflète plus de manière adéquate la complexité et l'hétérogénéité des motivations des agents publics. Basée sur des données empiriques qualitatives et quantitatives, une typologie originale des motivations dans l'univers post-bureaucratique est développée et testée dans plusieurs organisations publiques suisses. Elle révèle des facteurs de motivations qui combinent de manière originale des éléments classiques de la bureaucratie avec d'autres sources de motivation caractéristiques de formes modernes d'administration publique.

Techniques for CT and MR, post-processing, radiation

Brain perfusion can be assessed by CT and MR. For CT, two major techniques are used. First, Xenon CT is an equilibrium technique based on a freely diffusible tracer. First pass of iodinated contrast injected intravenously is a second method, more widely available. Both methods are proven to be robust and quantitative, thanks to the linear relationship between contrast concentration and x-ray attenuation. For the CT methods, concern regarding x-ray doses delivered to the patients need to be addressed. MR is also able to assess brain perfusion using the first pass of gadolinium based contrast agent injected intravenously. This method has to be considered as a semi-quantitative because of the non linear relationship between contrast concentration and MR signal changes. Arterial spin labeling is another MR method assessing brain perfusion without injection of contrast. In such case, the blood flow in the carotids is magnetically labelled by an external radiofrequency pulse and observed during its first pass through the brain. Each of this various CT and MR techniques have advantages and limits that will be illustrated and summarized.Learning Objectives:1. To understand and compare the different techniques for brain perfusion imaging.2. To learn about the methods of acquisition and post-processing of brain perfusion by first pass of contrast agent for CT and MR.3. To learn about non contrast MR methods (arterial spin labelling).

Individualiser la thérapie d'exposition pour le stress post-traumatique: le cas de Caroline

Dans la thérapie de l'état de stress post-traumatique chronique (PTSD), l'Exposition Prolongée (PE) à des stimuli associes à une expérience d'origine traumatique est considérée comme une méthode de traitement de pointe. Notre étude de cas, basée sur l'utilisation du manuel de Foa et Rothbaum (1998), concerne Caroline, une patiente adulte victime d'abus sexuels dans l'enfance, traitée en 40 séances, sur une durée d'une année. En complément, nous avons la technique de l'«Analyse des Plans» de Caspar (1995, 2007) pour la formulation de cas individualisée et la planification du traitement, selon le concept de Caspar de la Relation Thérapeutique Orientée sur les Motifs (MOTR). Le traitement a été très efficace, comme l'attestent les mesures quantitatives standardisées, les changements dans les schémas de comportements, ainsi que son compte rendu subjectif. Une analyse du processus thérapeutique illustre l'importance d'une combinaison de procédures basées sur un manuel avec des formulations et interventions de cas individuels. Le cas est discute dans le contexte de l'amélioration du traitement cognitivo-comportemental du PTSD.

Effects of exercise on the secondary blood markers commonly used to suspect erythropoietin doping.

Numerous trials have reported that some haematological and biochemical parameters could be put together and be used to detect and fight recombinant erythropoietin doping. Unfortunately, none of the studies mentioned the necessity of taking pre-analytical precautions to avoid possible suspicious results coming from major plasma volume changes caused notably by dehydration. Therefore we studied the behaviour of the most common secondary blood markers before and after a strenuous physical activity to find out how reliable these parameters were. The soluble transferrin receptor and the haemoglobin concentrations as well as the haematocrit level increased significantly after effort, whereas the plasma EPO concentration and the reticulocyte count remained constant. On the other hand, if the values were corrected for haemoconcentration, the soluble transferrin receptor concentration remained stable.

Gastric banding induces negative bone remodelling in the absence of secondary hyperparathyroidism: potential role of serum C telopeptides for follow-up.

OBJECTIVE: Data about the consequences of laparoscopic adjustable gastric banding (LAGB) on phospho-calcic and bone metabolism remain scarce. SUBJECTS: We studied a group of 37 obese premenopausal women (age: 24-52 y; mean BMI = 43.7 kg/m2) who underwent LAGB. METHODS: Serum calcium, phosphate, alkaline phosphatase, parathormone (PTH), vitamin D3, serum C-telopeptides, IGFBP-3 and IGF-1 were measured at baseline, 6, 12, 18 and 24 months after surgery. Body composition, bone mineral content (BMC) and density (BMD) were measured using dual-X-ray absorptiometry (DXA) at baseline, 6, 12 and 24 months after surgery. RESULTS: There was no clinically significant decrease of calcemia; PTH remained stable. Serum telopeptides increased by 100% (P < 0.001) and serum IGFBP-3 decreased by 16% (P < 0.001) during the first 6 months, and then stabilized, whereas IGF-1 remained stable over the 2 y. BMC and BMD decreased, especially at the femoral neck; this decrease was significantly correlated with the decrease of waist and hip circumference. CONCLUSIONS: We concluded that there was no evidence of secondary hyperparathyroidism 24 months after LAGB. The observed bone resorption could be linked to the decrease of IGFBP-3, although this decrease could be attributable to other confounding factors. Serum telopeptides seem to be a reliable marker of bone metabolism after gastric banding. DXA must be interpreted cautiously during major weight loss, because of the artefacts caused by the important variation of fat tissue after LAGB.

In Vivo Modulation of Mitochondrial Activity Determines HSC Engraftment and Post-Transplant Survival in Mice

Cellular metabolism is emerging as a potential fate determinant in cancer and stem cell biology, constituting a crucial regulator of the hematopoietic stem cell (HSC) pool [1-4]. The extremely low oxygen tension in the HSC microenvironment of the adult bone marrow forces HSCs into a low metabolic profile that is thought to enable their maintenance by protecting them from reactive oxygen species (ROS). Although HSC quiescence has for long been associated with low mitochondrial activity, as testified by the low rhodamine stain that marks primitive HSCs, we hypothesized that mitochondrial activation could be an HSC fate determinant in its own right. We thus set to investigate the implications of pharmacologically modulating mitochondrial activity during bone marrow transplantation, and have found that forcing mitochondrial activation in the post-transplant period dramatically increases survival. Specifically, we examined the mitochondrial content and activation profile of each murine hematopoietic stem and progenitor compartment. Long-term-HSCs (LT-HSC, Lin-cKit+Sca1+ (LKS) CD150+CD34-), short-term-HSCs (ST-HSC, LKS+150+34+), multipotent progenitors (MPPs, LKS+150-) and committed progenitors (PROG, Lin-cKit+Sca1-) display distinct mitochondrial profiles, with both mitochondrial content and activity increasing with differentiation. Indeed, we found that overall function of the hematopoietic progenitor and stem cell compartment can be resolved by mitochondrial activity alone, as illustrated by the fact that low mitochondrial activity LKS cells (TMRM low) can provide efficient long-term engraftment, while high mitochondrial activity LKS cells (TMRM high) cannot engraft in lethally irradiated mice. Moreover, low mitochondrial activity can equally predict efficiency of engraftment within the LT-HSC and ST-HSC compartments, opening the field to a novel method of discriminating a population of transitioning ST-HSCs that retain long-term engraftment capacity. Based on previous experience that a high-fat bone marrow microenvironment depletes short-term hematopoietic progenitors while conserving their long-term counterparts [5], we set to measure HSC mitochondrial activation in high-fat diet fed mice, known to decrease metabolic rate on a per cell basis through excess insulin/IGF-1 production. Congruently, we found lower mitochondrial activation as assessed by flow cytometry and RT-PCR analysis as well as a depletion of the short-term progenitor compartment in high fat versus control chow diet fed mice. We then tested the effects of a mitochondrial activator known to counteract the negative effects of high fat diet. We first analyzed the in vitro effect on HSC cell cycle kinetics, where no significant change in proliferation or division time was found. However, HSCs responded to the mitochondrial activator by increasing asynchrony, a behavior that is thought to directly correlate with asymmetric division [6]. As opposed to high-fat diet fed mice, mice fed with the mitochondrial activator showed an increase in ST-HSCs, while all the other hematopoietic compartments were comparable to mice fed on control diet. Given the dependency on short-term progenitors to rapidly reconstitute hematopoiesis following bone marrow transplantation, we tested the effect of pharmacological mitochondrial activation on the recovery of mice transplanted with a limiting HSC dose. Survival 3 weeks post-transplant was 80% in the treated group compared to 0% in the control group, as predicted by faster recovery of platelet and neutrophil counts. In conclusion, we have found that mitochondrial activation regulates the long-term to short-term HSC transition, unraveling mitochondrial modulation as a valuable drug target for post-transplant therapy. Identification of molecular pathways accountable for the metabolically mediated fate switch is currently ongoing.

GLUT2 surface expression and intracellular transport via the constitutive pathway in pancreatic beta cells and insulinoma: evidence for a block in trans-Golgi network exit by brefeldin A.

The biosynthesis, intracellular transport, and surface expression of the beta cell glucose transporter GLUT2 was investigated in isolated islets and insulinoma cells. Using a trypsin sensitivity assay to measure cell surface expression, we determined that: (a) greater than 95% of GLUT2 was expressed on the plasma membrane; (b) GLUT2 did not recycle in intracellular vesicles; and (c) after trypsin treatment, reexpression of the intact transporter occurred with a t1/2 of approximately 7 h. Kinetics of intracellular transport of GLUT2 was investigated in pulse-labeling experiments combined with glycosidase treatment and the trypsin sensitivity assay. We determined that transport from the endoplasmic reticulum to the trans-Golgi network (TGN) occurred with a t1/2 of 15 min and that transport from the TGN to the plasma membrane required a similar half-time. When added at the start of a pulse-labeling experiment, brefeldin A prevented exit of GLUT2 from the endoplasmic reticulum. When the transporter was first accumulated in the TGN during a 15-min period of chase, but not following a low temperature (22 degrees C) incubation, addition of brefeldin A (BFA) prevented subsequent surface expression of the transporter. This indicated that brefeldin A prevented GLUT2 exit from the TGN by acting at a site proximal to the 22 degrees C block. Together, these data demonstrate that GLUT2 surface expression in beta cells is via the constitutive pathway, that transport can be blocked by BFA at two distinct steps and that once on the surface, GLUT2 does not recycle in intracellular vesicles.

Self-reported health needs and use of primary health care services by adolescents enrolled in post-mandatory schools or vocational training programmes in Switzerland.

BACKGROUND: The second Swiss Multicenter Adolescent Survey on Health (SMASH02) was conducted among a representative sample (n = 7428) of students and apprentices aged 16 to 20 from the three language areas of Switzerland during the year 2002. This paper reports on health needs expressed by adolescents and their use of health care services over the 12 months preceding the survey. METHODS: Nineteen cantons representing 80% of the resident population agreed to participate. A complex iterative random cluster sample of 600 classes was drawn with classes as primary sampling unit. The participation rate was 97.7% for the classes and 99.8% for the youths in attendance. The self-administered questionnaire included 565 items. The median rate of item non-response was 1.8%. Ethical and legal requirements applying to surveys of adolescent populations were respected. RESULTS: Overall more than 90% of adolescents felt in good to excellent health. Suffering often or very often from different physical complaints or pain was also reported such as headache (boys: 15.9%, girls: 37.4%), stomach-ache (boys: 9.7%, girls: 30.0%), joint pain (boys: 24.7%, girls: 29.5%) or back pain (boys: 24.3%, girls: 34.7%). Many adolescents reported a need for help on psychosocial and lifestyle issues, such as stress (boys: 28.5%, girls: 47.7%) or depression (boys: 18.9%, girls: 34.4%). Although about 75% of adolescents reported having consulted a general practitioner and about one-third having seen another specialist, reported reasons for visits do not correspond to the expressed needs. Less than 10% of adolescents had visited a psychiatrist, a family planning centre or a social worker. CONCLUSIONS: The reported rates of health services utilisation by adolescents does not match the substantial reported needs for help in various areas. This may indicate that the corresponding problems are not adequately detected and/or addressed by professionals from the health and social sectors.